tbuckley/cabot-search huggingface dataset:
Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial
Authors: Riccardo Masson, Maria Mazurkiewicz-Bełdzińska, Kristy Rose, Laurent Servais, Hui Xiong, Edmar Zanoteli, Giovanni Baranello, Claudio Bruno, John W Day, Nicolas Deconinck, Andrea Klein, Eugenio Mercuri, Dmitry Vlodavets, Yi Wang, Angela Dodman, Muna El-Khairi, Ksenija Gorni, Birgit Jaber, Heidemarie Kletzl, Eleni Gaki, Paulo Fontoura, Basil T Darras, Joseph J Volpe, John Posner, Ulrich Kellner, Rosaline Quinlivan, Marianne Gerber, Omar Khwaja, Renata S Scalco, Timothy Seabrook, Armin Koch, Irina Balikova, Inge Joniau, Geraldine Accou, Valentine Tahon, Sylvia Wittevrongel, Elke De Vos, Rodrigo de Holanda Mendonça, Ciro Matsui Jr, Ana Letícia Fornazieri Darcie, Cleide Machado, Maria Kiyoko Oyamada, Joyce Martini, Graziela Polido, Juliana Rodrigues Iannicelli, Juliana Caires de Oliveira Achili Ferreira, Chaoping Hu, Xiaomei Zhu, Chen Qian, Li Shen, Hui Li, Yiyun Shi, Shuizhen Zhou, Ying Xiao, Zhenxuan Zhou, Sujuan Wang, Tian Sang, Cuijie Wei, Hui Dong, Yiwen Cao, Jing Wen, Wenzhu Li, Lun Qin, Nina Barisic, Ivan Celovec, Martina Galiot Delic, Petra Kristina Ivkic, Nenad Vukojevic, Ivana Kern, Boris Najdanovic, Marin Skugor, Josipa Tomas, Odile Boespflug-Tanguy, Silvana De Lucia, Andrea Seferian, Emmanuel Barreau, Nabila Mnafek, Helene Peche, Allison Grange, Diem Trang Nguyen, Darko Milascevic, Shotaro Tachibana, Emanuela Pagliano, Stefania Bianchi Marzoli, Diletta Santarsiero, Myriam Garcia Sierra, Gemma Tremolada, Maria Teresa Arnoldi, Marta Vigano, Claudia Dosi, Riccardo Zanin, Veronica Schembri, Noemi Brolatti, Giuseppe Rao, Elisa Tassara, Simone Morando, Paola Tacchetti, Marina Pedemonte, Enrico Priolo, Lorenza Sposetti, Giacomo Pietro Comi, Alessandra Govoni, Silvia Gabriella Osnaghi, Valeria Minorini, Francesca Abbati, Federica Fassini, Michaela Foa, Amalia Lopopolo, Marika Pane, Concetta Palermo, Maria Carmela Pera, Giulia Maria Amorelli, Costanza Barresi, Guglielmo D'Amico, Lorenzo Orazi, Giorgia Coratti, Daniela Leone, Antonaci Laura, Roberto De Sanctis, Beatrice Berti, Naoki Kimura, Yasuhiro Takeshima, Hideki Shimomura, Tomoko Lee, Fumi Gomi, Takanobu Morimatsu, Toru Furukawa, Urszula Stodolska-Koberda, Agnieszka Waskowska, Jagoda Kolendo, Agnieszka Sobierajska-Rek, Sandra Modrzejewska, Anna Lemska, Evgenia Melnik, Svetlana Artemyeva, Natalya Leppenen, Nataliya Yupatova, Anastasya Monakhova, Yulia Papina, Olga Shidlovsckaia, Elena Litvinova, Cornelia Enzmann, Elea Galiart, Konstantin Gugleta, Christine Wondrusch Haschke, Haluk Topaloglu, Ibrahim Oncel, Nesibe Eroglu Ertugrul, Bahadir Konuskan, Bora Eldem, Sibel Kadayifçilar, Ipek Alemdaroglu, Seher Sari, Neslihan Bilgin, Aynur Ayse Karaduman, Fatma Gokcem Yildiz Sarikaya, Robert J Graham, Partha Ghosh, David Casavant, Alexis Levine, Rachael Titus, Amanda Engelbrekt, Lucia Ambrosio, Anne Fulton, Anna Maria Baglieri, Courtney Dias, Elizabeth Maczek, Amy Pasternak, Shannon Beres, Tina Duong, Richard Gee, Sally Young
Journal: The Lancet Neurology (2022)
Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study
Authors: Zev A Wainberg, Peter C Enzinger, Yoon-Koo Kang, Shukui Qin, Kensei Yamaguchi, In-Ho Kim, Anwaar Saeed, Sang Cheul Oh, Jin Li, Haci Mehmet Turk, Alexandra Teixeira, Christophe Borg, Erika Hitre, Adrian A Udrea, Giovanni Gerardo Cardellino, Raquel Guardeño Sanchez, Helen Collins, Siddhartha Mitra, Yingsi Yang, Daniel V T Catenacci, Keun-Wook Lee
Journal: The Lancet Oncology (2022)
Cardiac-targeted PIASy gene silencing mediates deSUMOylation of caveolin-3 and prevents ischemia/reperfusion-induced Nav1.5 downregulation and ventricular arrhythmias
Authors: Chen-Chen Hu, Xin Wei, Jin-Min Liu, Lin-Lin Han, Cheng-Kun Xia, Jing Wu, Tao You, A.-Fang Zhu, Shang-Long Yao, Shi-Ying Yuan, Hao-Dong Xu, Zheng-Yuan Xia, Ting-Ting Wang, Wei-Ke Mao
Journal: Military Medical Research (2022)

Abnormal myocardial Nav1.5 expression and function cause lethal ventricular arrhythmias during myocardial ischemia-reperfusion (I/R). Protein inhibitor of activated STAT Y (PIASy)-mediated caveolin-3 (Cav-3) SUMO modification affects Cav-3 binding to the voltage-gated sodium channel 1.5 (Nav1.5). PIASy activity is increased after myocardial I/R, but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias. Using recombinant adeno-associated virus subtype 9 (AAV9), rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA (shRNA). After two weeks, rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias. Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements. PIASy was upregulated by I/R (P < 0.01), with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density (P < 0.01). AAV9-PIASy shRNA intraventricular injection into the rat heart downregulated PIASy after I/R, at both mRNA and protein levels (P < 0.05 vs. Scramble-shRNA + I/R group), decreased SUMO-modified Cav-3 levels, enhanced Cav-3 binding to Nav1.5, and prevented I/R-induced decrease of Nav1.5 and Cav-3 co-localization in the intercalated disc and lateral membrane. PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias, which was reflected by a modest decrease in the duration of ventricular fibrillation (VF; P < 0.05 vs. Scramble-shRNA + I/R group) and a significantly reduced arrhythmia score (P < 0.01 vs. Scramble-shRNA + I/R group). The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia (VT), sustained VT and VF, especially at the time 5-10 min after ischemia (P < 0.05 vs. Scramble-shRNA + IR group). Using in vitro human embryonic kidney 293 T (HEK293T) cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation (H/R), we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R. Mutation of SUMO consensus lysine sites in Cav-3 (K38R or K144R) altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells. I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias. Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes, and subsequent ventricular arrhythmias in rats. PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.
Erratum. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study. Diabetes Care 2021;44:1433–1442
Authors: Rajaa Nahra, Tao Wang, Kishore M. Gadde, Jan Oscarsson, Michael Stumvoll, Lutz Jermutus, Boaz Hirshberg, Philip Ambery
Journal: Diabetes Care (2022)

In the article cited above, the y-axis in Fig. 3C was incorrectly labeled “% Change in FIB-4 Index.” The correct label is “Mean change in FIB-4 index.” Fig. 3C and its corresponding legend text have been amended accordingly. In addition, the legend text for Fig. 3D did not match the data reported. Panel D represents mean change, not percent change, in NAFLD fibrosis score (NFS). The legend text has been corrected to read “D: Mean change in NFS.” As a result of these changes, the title of Fig. 3 has been amended from “Percent change in hepatic parameters from baseline to week 54” to “Change in hepatic parameters from baseline to week 54.” The authors apologize for the errors. The online version of the article (https://doi.org/10.2337/dc20-2151) has been updated to correct the errors.
Cortical sensory processing across motivational states during goal-directed behavior
Authors: Giulio Matteucci, Maëlle Guyoton, Johannes M. Mayrhofer, Matthieu Auffret, Georgios Foustoukos, Carl C.H. Petersen, Sami El-Boustani
Journal: Neuron (2022)

Behavioral states can influence performance of goal-directed sensorimotor tasks. Yet, it is unclear how altered neuronal sensory representations in these states relate to task performance and learning. We trained water-restricted mice in a two-whisker discrimination task to study cortical circuits underlying perceptual decision-making under different levels of thirst. We identified somatosensory cortices as well as the premotor cortex as part of the circuit necessary for task execution. Two-photon calcium imaging in these areas identified populations selective to sensory or motor events. Analysis of task performance during individual sessions revealed distinct behavioral states induced by decreasing levels of thirst-related motivation. Learning was better explained by improvements in motivational state control rather than sensorimotor association. Whisker sensory representations in the cortex were altered across behavioral states. In particular, whisker stimuli could be better decoded from neuronal activity during high task performance states, suggesting that state-dependent changes of sensory processing influence decision-making.
HIV Stigma and Health Care Discrimination Experienced by Hispanic or Latino Persons with HIV — United States, 2018–2020
Authors: Mabel Padilla, Deesha Patel, Linda Beer, Yunfeng Tie, Priya Nair, Yamir Salabarría-Peña, Kirk D. Henny, Dominique Thomas, Sharoda Dasgupta
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Hispanic or Latino (Hispanic) persons with HIV experience disparities in HIV health outcomes compared with some other racial and ethnic groups. A previous report found that the percentages of Hispanic persons who received HIV care, were retained in care, and were virally suppressed were lower than those among non-Hispanic White persons with HIV (1). HIV stigma and discrimination are human rights issues associated with adverse HIV outcomes; eliminating stigma and discrimination among persons with HIV is a national priority*,†,§ (2,3). CDC analyzed data from the Medical Monitoring Project (MMP), an annual, cross-sectional study designed to report nationally representative estimates of experiences and outcomes among adults with diagnosed HIV. Data from the 2018-2020 cycles were analyzed to assess self-reported stigma and health care discrimination using adapted versions of validated multi-component scales among 2,690 adult Hispanic persons with HIV in the United States overall and by six characteristics.¶ The median HIV stigma score on a scale of 0-100 was 31.7, with women (35.6) and American Indian or Alaska Native (AI/AN) persons (38.9) reporting the highest scores among Hispanic persons with HIV. HIV stigma was primarily attributed to disclosure concerns (e.g., fearing others will disclose one's HIV status and being careful about who one tells about one's HIV status). Nearly one in four (23%) Hispanic persons with HIV experienced health care discrimination. Health care discrimination was experienced more frequently by Hispanic men (23%) than by Hispanic women (18%) and by Black or African American (Black) Hispanic persons (28%) than by White Hispanic persons (21%). Understanding disparities in experiences of stigma and discrimination is important when designing culturally appropriate interventions to reduce stigma and discrimination.
A surface-receptor-coupled G protein regulates plant immunity through nuclear protein kinases
Authors: Miaomiao Ma, Wei Wang, Yue Fei, Hang-Yuan Cheng, Beibei Song, Zhaoyang Zhou, Yan Zhao, Xiaojuan Zhang, Lin Li, She Chen, Jizong Wang, Xiangxiu Liang, Jian-Min Zhou
Journal: Cell Host & Microbe (2022)
Spatial epitope barcoding reveals clonal tumor patch behaviors
Authors: Xavier Rovira-Clavé, Alexandros P. Drainas, Sizun Jiang, Yunhao Bai, Maya Baron, Bokai Zhu, Alec E. Dallas, Myung Chang Lee, Theresa P. Chu, Alessandra Holzem, Ramya Ayyagari, Debadrita Bhattacharya, Erin F. McCaffrey, Noah F. Greenwald, Maxim Markovic, Garry L. Coles, Michael Angelo, Michael C. Bassik, Julien Sage, Garry P. Nolan
Journal: Cancer Cell (2022)

Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitopes for imaging using combinatorial tagging (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using EpicMIBI, we dissected the spatial component of cell lineages and phenotypes in xenograft models of small cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of clonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in these models. In a tumor model harboring a fraction of PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells. EpicMIBI facilitates in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.
Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells
Authors: Xingying Zhang, Chenze Zhang, Miaomiao Qiao, Chen Cheng, Na Tang, Shan Lu, Wen Sun, Beilei Xu, Yuanwei Cao, Xiaofei Wei, Yao Wang, Weidong Han, Haoyi Wang
Journal: Cancer Cell (2022)
BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass
Authors: Jennifer Hampton Hill, Michelle Sconce Massaquoi, Emily Goers Sweeney, Elena S. Wall, Philip Jahl, Rickesha Bell, Karen Kallio, Daniel Derrick, L. Charles Murtaugh, Raghuveer Parthasarathy, S. James Remington, June L. Round, Karen Guillemin
Journal: Cell Metabolism (2022)
The gut peptide Reg3g links the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function
Authors: Jae Hoon Shin, Nadejda Bozadjieva-Kramer, Yikai Shao, Sally Lyons-Abbott, Alan C. Rupp, Darleen A. Sandoval, Randy J. Seeley
Journal: Cell Metabolism (2022)
Ecosystem consequences of herbicides: the role of microbiome
Authors: Suvi Ruuskanen, Benjamin Fuchs, Riitta Nissinen, Pere Puigbò, Miia Rainio, Kari Saikkonen, Marjo Helander
Journal: Trends in Ecology & Evolution (2022)

Non-target organisms are globally exposed to herbicides. While many herbicides - for example, glyphosate - were initially considered safe, increasing evidence demonstrates that they have profound effects on ecosystem functions via altered microbial communities. We provide a comprehensive framework on how herbicide residues may modulate ecosystem-level outcomes via alteration of microbiomes. The changes in soil microbiome are likely to influence key nutrient cycling and plant-soil processes. Herbicide-altered microbiome affects plant and animal performance and can influence trophic interactions such as herbivory and pollination. These changes are expected to lead to ecosystem and even evolutionary consequences for both microbes and hosts. Tackling the threats caused by agrochemicals to ecosystem functions and services requires tools and solutions based on a comprehensive understanding of microbe-mediated risks.
Dissemination of circulating tumor cells at night: role of sleep or circadian rhythm?
Authors: Yves Dauvilliers, Frédéric Thomas, Catherine Alix-Panabières
Journal: Genome biology (2022)

The analysis of blood for circulating tumor cells (CTCs) called liquid biopsy has opened new avenues for cancer diagnostic and management, as well as the comprehension of the metastatic cascade [1].As metastasis is responsible for about 90% of cancer deaths [2], it is of utmost importance to decrease the survival of CTCs, mostly to target specifically the metastasis-competent CTCs while they are reaching distant organs [3].How CTCs are disseminating through the bloodstream?In advanced cancers, CTCs can travel as clusters or microemboli in the blood.CTCs traveling in a group seem to be released from hypoxic tumor regions [4] and clearly present a specific hypomethylation pattern related to stem cell features, underlying their higher aggressiveness [5].Consequently, CTC clusters predict a poorer prognosis compared to single CTCs.Interestingly, CTC microemboli can also include other cell types, such as immune cells and/or cancer-associated fibroblasts from the tumor microenvironment, which have a higher capacity to survive and to metastasize.When CTCs are traveling the most?This specific question has already arised in 2020 when Cortés-Hernández et al. hypothesized that, because of evolutionary ecology reasons, malignant cells, including CTCs, should behave differently between day and night [6].The recent work of Diamantopoulou et al. showed that the levels of CTCs increased at night in humans with breast cancer and mouse models of breast cancer and that CTCs in the rest-phase are more likely to metastasize [7].This non-continuous generation of CTCs within the rest phase, if confirmed, will undoubtedly have major medical implications.However, key questions remain at this stage: Is it sleep and/or the circadian rhythm involved in the formation of CTCs and the metastatic spread of cancer, and by which specific mechanisms?The biology of most, if not all, living things is regulated by biological rhythms, in particular sleep and the circadian rhythm [8].Due to the extreme diversity of cells typically generated in tumors, natural selection acting on cells, and/or groups of cells, may
Specific <scp>IgE</scp> against the house dust mite allergens Der p 5, 20 and 21 influences the phenotype and severity of atopic diseases
Authors: Theresa Walsemann, Marisa Böttger, Stephan Traidl, Christian Schwager, Askin Gülsen, Sina Freimooser, Lennart Matthias Roesner, Thomas Werfel, Uta Jappe
Journal: Allergy (2022)

House dust mites (HDM) are among the most important sources for airborne allergens with high relevance for atopic diseases. Routine tests contain only 4 of 32 registered allergens of Dermatophagoides pteronyssinus. Clinical relevance and pathomechanistic properties of many allergens are not well understood.The association of several HDM allergens with allergic rhinitis, allergic asthma, and atopic dermatitis was investigated to identify allergens with biomarker potential and to transfer them into diagnostics.Eight out of nine D. pteronyssinus allergens (nDer p 1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer p 13, rDer p 20, rDer p 21, rDer p 23) were recombinantly expressed and purified. Sensitization patterns of 384 HDM-allergic individuals exhibiting different clinical phenotypes were analyzed with a serum-saving multiplex array.Sensitization to more than three mite allergens (sensitization count) was associated with allergic asthma and/or atopic dermatitis. Reactions to Der p 5 and Der p 21 were more frequent in allergic asthma compared to allergic rhinitis. Atopic dermatitis patients were more often sensitized to Der p 5, Der p 20, and Der p 21 among others. Der p 20-IgE > 80 kU/L was associated with severe atopic dermatitis in 75% of patients.This study demonstrates the clinical importance of the sensitization count and of certain allergens (Der p 5, Der p 20, and Der p 21) not available for routine diagnostics yet. Implementing them as well as the sensitization count in diagnostic measures will improve diagnosis and risk assessment of HDM-allergic patients.
Correction: Synergistic Killing Effect Between Vorinostat and Target of CD146 in Malignant Cells
Authors: Xiaoli Ma, Jia Liu, Jiang Wu, Xiyun Yan, Peng Wu, Yong Liu, Shuang Li, Yuan Tian, Yang Cao, Gang Chen, Li Meng, Gang Xu, Shixuan Wang, Yunping Lu, Ding Ma, Jianfeng Zhou
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), Fig. 5E Vorinstat+mIgG had a blank space caused by tissue removal that the authors covered using a portion of the same IHC for aesthetic purposes. The error has been corrected using the original unmodified image in the latest online HTML and PDF versions of the article. The authors regret the error.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Metastatic progression of Ewing sarcoma requires that activity of its oncogenic driver, EWS:: FLI1, be moderated.Apfelbaum and colleagues have identified HOXD13 as a tumor-specific regulator of EWS::FLI1 activity.Transcriptomic and epigenomic studies showed that EWS:: FLI1 directly activates HOXD13 and that antagonism between these transcription factors determines mesenchymal cell state.In particular, cells with high HOXD13 activity selectively activated mesenchymal programs that are repressed by EWS::FLI1.These studies demonstrate the importance of cell context-dependent transcription factors as moderators of fusion gene activity and phenotypic cell state.Future studies are indicated to determine if these transcriptionally distinct cell states define metastasis-initiating cells.
Correction: Clinical Significance of <i>PIK3CA</i> and <i>ESR1</i> Mutations in Circulating Tumor DNA: Analysis from the MONARCH 2 Study of Abemaciclib plus Fulvestrant
Authors: Sara M. Tolaney, Masakazu Toi, Patrick Neven, Joohyuk Sohn, Eva-Maria Grischke, Antonio Llombart-Cussac, Hatem Soliman, Hong Wang, Sameera Wijayawardana, Valerie M. Jansen, Lacey M. Litchfield, George W. Sledge
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), the upper and lower limits for the confidence intervals for the ESR1-mutant subgroup were incorrect in Fig. 2, in the Abstract, and in the Results section of the article. The errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret the errors.
Correction: Functional Categorization of <i>BRCA1</i> Variants of Uncertain Clinical Significance in Homologous Recombination Repair Complementation Assays
Authors: Peter Bouwman, Ingrid van der Heijden, Hanneke van der Gulden, Roebi de Bruijn, Merel E. Braspenning, Setareh Moghadasi, Lodewyk F.A. Wessels, Maaike P.G. Vreeswijk, Jos Jonkers
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), the combined LR for BRCA1 variant of uncertain clinical significance c.5216A>G was listed as 0.012927147 due to a calculation error in Supplementary Table S4. Because the correct combined LR of 0.836732119 is between 0.5 and 2.0, no posterior probability should have been calculated and the variant should not have been included in Fig. 5 and in the calculated variant totals relayed in the Abstract, Results, and Discussion sections. While the calculation for BRCA1 c.5216A>G was incorrect, it was not misclassified, that is, it remains a variant of uncertain clinical significance. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret the error.